ORIGINAL ARTICLE
Growth patterns and body composition in former extremely low birth
weight (ELBW) neonates until adulthood: a systematic review
Caroline Van de Pol1 &Karel Allegaert2,3
Received: 25 June 2019 / Revised: 10 December 2019 / Accepted: 12 December 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract
Preterm infants are obviously born lighter and shorter, with smaller head circumferences than normal birth weight term born neonates. They also have a different body composition. Compromised growth is associated with adverse health outcomes. Both growth retardation and accelerated growth are suggested to cause metabolic, cardiovascular, and renal complications. Reviews regarding growth and body composition in preterm infants often do not differen-tiate between birth weight and gestational age. The purpose of this systematic review is to assemble growth data, specific in extremely low birth weight children. Different databases were searched for studies regarding growth and body composition in former extremely low birth weight infants until adulthood. We compared height, weight, head circumference, body mass index, fat mass, lean mass, fat distribution, and body water to matched normal birth weight controls and the World Health Organization growth charts. Studies consistently reported that former extreme-ly low birth weight neonates experience a period of accelerated postnatal growth, but they achieve lower anthropo-metric parameters than normal birth weight children. There is no consensus about differences in body composition and how to measure this.
Conclusion: Although extremely low birth weight infants exhibit a period of catch-up growth, their growth remains retarded later in life. Further research is needed to investigate body composition and the associated risk of cardiovascular diseases or metabolic syndrome.
What is Known:
• Extremely low birth weight infants have lower anthropometric parameters and a different body composition at birth and term-corrected age than normal birth weight infants.
• Former extremely low birth weight infants also have a higher risk on adverse cardiovascular health outcomes in later life. What is New:
• After hospital discharge, extremely low birth weight neonates remain smaller and probably also lighter, with smaller head circumferences at each corrected age throughout childhood and adolescence when compared to normal birth weight infants or the World Health Organization growth charts. It is not clear whether extremely low birth weight infants reach a lower or similar body mass index score as normal birth weight infants.
• There is a lack of (long-term) information on body composition in extremely low birth weight infants.
Keywords Anthropometry . Body composition . Extremely low birth weight . Fat distribution . Growth . Total body fat Abbreviations
AGA Appropriate for gestational age BMI Body mass index
BW Birth weight CA Corrected age
CPEG Canadian Pediatric Endocrine Group ELBW Extremely low birth weight
FM Fat mass
FMI Fat mass index %FM Percentage fat mass GA Gestational age HC Head circumference * Karel Allegaert
karel.allegaert@uzleuven.be Caroline Van de Pol
caroline.vandepol@gmail.com 1
KU Leuven, Leuven, Belgium 2
Department of Development and Regeneration, and Department of Pharmaceutical and Pharmacological Sciences Organ Systems, KU Leuven, Leuven, Belgium
3 Department of Clinical Pharmacy, Erasmus MC, Erasmus MC,
Rotterdam, The Netherlands https://doi.org/10.1007/s00431-019-03552-z
LM Lean mass LMI Lean mass index %LM Percentage lean mass NBW Normal birth weight TBF Total body fat
%TBF Percentage total body fat TBW Total body water
%TBW Percentage total body water SGA Small for gestational age TCA Term corrected age WHO World Health Organization SSE Sum of squared estimate of errors RMSE Root mean square error
Introduction
Growth patterns and body development are relevant in pre-term infants, likely most relevant in extremely low birth weight (ELBW, i.e., <1 kg) infants. Infants born preterm are lighter and shorter, with a smaller head circumference (HC) than their term born normal birth weight (NBW) peers, at birth as well as when they reach term-corrected age (TCA) and throughout childhood [1,2]. When preterm infants are classi-fied by weight, as ELBW infants, they are often small for their gestational age (SGA) [3]. This makes them even more sus-ceptible to effects of perinatal growth retardation [4].
The perinatal growth retardation is followed by a period of catch-up growth, which usually starts in early infancy and can continue into early adolescence [5].
Preterm infants do not only have aberrant growth measure-ments but they also have a different body composition com-pared to term born neonates. Because the third trimester is a period of rapid adipose tissue deposition, they exhibit a fat distribution at TCA different than that of term born neonates. Preterm infants have a lower fat mass (FM) and an even more decreased lean mass (LM) at TCA, resulting in a greater per-centage total body fat (%TBF) than term born infants [2].
Low birth weight (LBW) infants, and even more ELBW infants are more susceptible to coronary heart diseases, neo-natal acute kidney injury, chronic kidney disease, type 2 dia-betes, stroke, and hypertension [6–8].
Although the effects of (early) infancy weight gain on later body composition and health outcomes are not clear, associa-tions with an aberrant fat distribution, cardiovascular diseases, and an obesity-associated exacerbation of renal risk have been suggested [8–12]. It is suggested that an altered body compo-sition that persists into adulthood could be a risk factor for developing metabolic and cardiovascular diseases, although it could not always be identified as a causal factor [3,5,9, 13,14]. However, the ideal growth pattern for ELBW infants is not yet known.
In addition, analyzing body composition could be useful for calculating drug doses and body composition parameters are used in some prediction models to determine maintenance doses [15].
Literature reviews regarding body composition after hospi-tal discharge and later in life are scarce and most do not dif-ferentiate between gestational age (GA) or birth weight (BW), although they might be important predictors of body compo-sition [16].
This systematic search focuses specifically on ELBW in-fants and investigates their growth patterns and body compo-sition after hospital discharge throughout infancy and adult-hood. Using a systematic review approach, we compared height, weight, HC, and body mass index (BMI) to control data of NBW peers and growth charts described by the World Health Organization (WHO) and the Canadian Pediatric Endocrine Group (CPEG). Parameters regarding body fat and fat distribution were compared to control data in the in-cluded studies.
Materials and methods
Study characteristics
Study design
We performed a systematic search and review including both prospective and retrospective longitudinal studies, as well as cross-sectional studies that describe data in cohorts of former ELBW neonates after hospital discharge until adulthood. There was no limit on minimum or maximum follow-up time. We only included observational studies. Intervention studies were excluded.
Language restrictions
Besides studies and abstracts that were available in English, studies written in a different language were included if they had an abstract or schematics available in English that contained the desired data.
Patients
We included studies concerning former ELBW infants. ELBW is defined as a BW less than 1000 g. ELBW infants are either SGA or appropriate for their GA (AGA). SGA is defined as a BW less than the 10th percentile for weight given the GA [17–22], but studies are heterogeneous as they some-times use different terms and definitions to indicate SGA. Intra-uterine growth restriction is also used as an analogous definition.
For control data, we simultaneously collected the data of control NBW (i.e., 2500–4000 g) infants matched by sex and age in the concerned study whenever available, and we com-pared the growth parameters to the WHO and CPEG growth charts [23–25].
Search strategy and selection process
A first search was performed by the first author in July 2018 and a second one in December 2018. Databases PubMed, Cochrane Library, Web of Science, and Embase were searched.
The extended search strategies for different databases and selection of the articles are represented in Table1and Fig.1, respectively [26]. The quality of the English studies was assessed using the “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies” of the National Heart, Lung and Blood Institute [27]. Studies were selected based on title and abstract, and the second author was consulted in case of uncertainties.
Outcome parameters and methodology applied
Parameters that were a component of growth or body compo-sition were extracted by the first author. In case of uncer-tainties, the second author was consulted. Extracted growth parameters are height, weight, HC, and BMI. Parameters re-garding body composition were either absolute (i.e., FM, LM, and total body water (TBW)) or relative (%TBF, percentage lean mass (%LM), and percentage total body water (%TBW)). We also investigated fat distribution.
Growth
We compared mean height, weight, HC, and BMI with data of NBW control children when available in the studies and with the 5th, 25th, and 50th percentile of the standard growth pa-rameters as described in the WHO Child Growth Standards and in the WHO Reference 2007 [23–25]. For weight-for-age after the age of 10, we compared with extended WHO refer-ence curves provided by the CPEG. Since these charts do not provide data for the 5th percentile, we compared to the 3th percentile instead [28].
We plotted the calculated weighted mean data of boys and girls against the WHO growth charts. The WHO data were calculated as the weighted mean of boys and girls equal to the ratio of male to female patients in the concerned studies at the compared age. We plotted growth data in graphs edited in MATLAB, while using a rational function based on the en-tered data [29]. Individual function characteristics of the graphs are described below the figures. The WHO growth charts are used to describe trends among the growth of
ELBW infants, but they were not statistically compared with the study data.
Different definitions of catch-up growth are used in the included studies. Catch-up growth is defined as a positive increase of the Z-score of >0.67 over a certain period of time [20, 30] or reaching growth parameters more than −2 SD scores for age [22,31].
Body composition
For FM, LM, %TBF, and %LM, we compared mean data of ELBW infants to control data as described in the included studies.
Methods to measure growth parameters and body composition
Studies were not excluded based on methods used for mea-suring growth parameters or body composition, as some of these methods are suggested to be more accurate but also more expensive or less applicable to newborn infants [14]. The use of these methodologies is further explained in the studies.
Results
There were 486 search results in PubMed, 33 trials in Cochrane Library, 383 in Embase, and 192 in Web of Science. Two studies that met the selection criteria were ex-cluded to avoid duplication (the study populations were also included in another more comprehensive included study) [32, 33]. Eventually, a total of 16 studies and one abstract were included. The selection process of the articles is represented in the PRISMA flow chart in Fig. 1 [26]. An overview of the included studies and the quality assessment are represented in Table2and Table3, respectively. One study had a very low follow-up rate with a small remaining study sample and was therefore not used for the WHO comparison [38]. Results of growth compared to controls are represented in Table4and those of body composition data in Table5.
Growth
Height
In almost every included study that compared ELBW infants to NBW infants, children and adults born with an ELBW remain smaller than NBW children, at every stage of their development [17–21,30,35–37,39–41]. Two studies found a difference between genders with a lower height in male infants at the age of 11 [41] and in female infants at the age of 14.7 [20]. Two studies suggested that ELBW infants attain
Table 1 Search strategies for different databases
Database Search strategy
Pubmed (("Extremely Low Birth Weight Infant"[Mesh] OR“Extremely low birth weight infant*”[tiab] OR “ELBW”[tiab] OR “Extremely Low Birth
Weight”[tiab])) AND (“Body Constitution"[Mesh/NoExp] OR “Body Constitution*"[tiab] OR “Body Distribution”[tiab] OR “Body weights and
measures”[Mesh/NoExp] OR “body weights and measures”[tiab] OR “Body Measure*”[tiab] OR “morphometry”[tiab] OR “Morphometrics”[tiab] OR
“Body Fat Distribution”[Mesh] OR “Body Fat Distribution”[tiab] OR “Body Fat Patterning”[tiab] OR “Adiposity”[tiab] OR “Adipose tissue
distribution”[tiab] OR “Fat tissue distribution”[tiab] OR “Fatty Tissue Distribution”[tiab] OR “Body Mass Index”[Mesh] OR “Body Mass Index”[tiab]
OR“Quetelet* Index”[tiab] OR “BMI”[tiab] OR “Body Size”[Mesh/NoExp] OR “Body Size*”[tiab] OR “Body Mass”[tiab] OR “Body
Height”[Mesh/NoExp] OR “Body Height*”[tiab] OR “Body length”[tiab] OR“Body Weight”[Mesh/NoExp] OR “Body Weight*”[tiab] OR “Total
Body Weight”[tiab] OR “Body Weight Changes”[Mesh/NoExp] OR “Body Weight Change*”[tiab] OR “Body Composition”[Mesh] OR “Body
Composition*”[tiab] OR “Body Water”[mesh] OR “body water”[tiab] OR “Whole Body Water”[tiab] OR “Total Water”[tiab] OR “Total Body
Water”[tiab] OR “Total Body Fluid”[tiab] OR “adipose tissue”[Mesh/NoExp] OR “Adipose Tissue*”[tiab] OR “Fat Tissue”[tiab] OR “Fatty
Tissue”[tiab] OR “Fat Pad*”[tiab] OR “Body Fat”[tiab] OR “body lipid”[tiab] OR “visceral fat distribution”[tiab] OR “Subcutaneous Fat
distribution”[tiab] OR “Anthropometry”[Mesh/NoExp] OR “Anthropometry”[tiab] OR “Anthropometric index”[tiab] OR “Anthropometrics”[tiab] OR
“Anthropometric parameters”[tiab] OR “Cephalometry”[mesh] OR “Cephalometry”[tiab] OR “Cephalometrics”[tiab] OR “Craniometry”[tiab] OR “Craniometrics”[tiab] OR “Head circumference”[tiab] OR “Cranial Circumference”[tiab] OR “Fat Mass”[tiab] OR “Fat Free Mass”[tiab] OR “Lean
Mass”[tiab] OR (“Postdischarge”[tiab] or “Postdischarge”[ tiab] AND (“growth”[mesh] OR “growth”[tiab])))
Cochrane Library
#1[mh“Extremely Low Birth Weight Infant”]
#2(“Extremely low Birth Weight Infant” or “ELBW” or “Extemely low birth weight”):ti,ab,kw
#3#1 OR #2
#4[mh ^”Body Constitution”] or [mh ^”Body Weights and measures”] or [mh “Body Fat Distribution”] or [mh “Body Mass Index”] or [mh ^”Body Size”]
or [mh ^”Body Height”] or [mh ^”Body Weight”] or [mh ^”Body Weight Changes”] OR [mh “Body Composition”] or [mh “Body Water”] or [mh
^”Adipose tissue”] or [mh ^”Anthropometry”] or [mh “Cephalometry”]
#5(“Body Constitution” or “Body Distribution” or “body weights and measures” or “Body Measure*” or “morphometry” or “Morphometrics” or “Body
Fat Distribution” or “Body Fat Patterning” or “Adiposity” or “Adipose tissue distribution” or “Fat tissue distribution” or “Fatty Tissue Distribution” or
“Body Mass Index” or “Quetelet* Index” or “BMI” or “Body Size*” or “Body Mass” or “Body Height*” or “Body length” or “Body Weight*” or “Total
Body Weight” or “Body Weight Change*” or “Body Composition*” or “body water” or “Whole Body Water” or “Total Water” or “Total Body Water” or
“Total Body Fluid” or “Adipose Tissue*” or “Fat Tissue” or “Fatty Tissue” or “Fat Pad*” or “Body Fat” or “body lipid” or “visceral fat distribution” or “Subcutaneous Fat distribution” or “Anthropometry” or “Anthropometric index” or “Anthropometrics” or “Anthropometric parameters” or “Cephalometry” or “Cephalometrics” or “Craniometry” or “Craniometrics” or “Head circumference” or “Cranial Circumference” or “Fat Mass” or “Fat
Free Mass” or “Lean Mass”):ti,ab,kw
#6(“Postdischarge” or “Post-Discharge”):ti,ab,kw #7[mh ^”Growth”] #8(“Growth”):ti,ab,kw #9#7 OR #8 #10#6 and #9 #11#5 OR #10 #12#4 OR #11 #13#3 AND #12
EMBASE (‘extremely low birth weight’/exp. OR ‘extremely low birth weight’:ti,ab OR ‘elbw’:ti,ab OR ‘extremely low birth weight infant*’:ti,ab) AND (‘body
constitution’/exp. OR ‘body constitution’:ti,ab OR ‘body distribution’:ti,ab OR ‘morphometry’/mj OR ‘morphometry’:ti,ab OR ‘morphometrics’:ti,ab
OR‘body weights and measures’:ti,ab OR ‘body measure*’:ti,ab OR ‘body composition’/exp. OR ‘body composition’:ti,ab OR ‘body fat’:ti,ab OR
‘body lipid’:ti,ab OR ‘fat load’:ti,ab OR ‘body fat distribution’:ti,ab OR ‘body fat patterning’:ti,ab OR ‘adipose tissue distribution’:ti,ab OR ‘fat tissue
distribution’:ti,ab OR ‘fatty tissue distribution’:ti,ab OR ‘subcutaneous fat distribution’:ti,ab OR ‘visceral fat distribution’:ti,ab OR ‘body water’:ti,ab
OR‘total water’:ti,ab OR ‘whole body water’:ti,ab OR ‘total body water’:ti,ab OR ‘total body fluid’:ti,ab OR ‘adipose tissue’/mj OR ‘adipose
tissue’:ti,ab OR ‘fat tissue’:ti,ab OR ‘fatty tissue’:ti,ab OR ‘fat pad’/exp. OR ‘fat pad*’:ti,ab OR ‘anthropometry’/mj OR ‘anthropometry’:ti,ab OR
‘anthropometric index’:ti,ab OR ‘anthropometrics’:ti,ab OR ‘antropometry’:ti,ab OR ‘body measurement’:ti,ab OR ‘cephalometry’/mj OR ‘cephalometry’:ti,ab OR ‘cephalometrics’:ti,ab OR ‘head size’:ti,ab OR ‘craniometry’/mj OR ‘craniometry’:ti,ab OR ‘craniometrics’:ti,ab OR ‘anthropometric parameters’/mj OR ‘anthropometric parameters’:ti,ab OR ‘body height’/exp. OR ‘body height’:ti,ab OR ‘body length’:ti,ab OR ‘body
weight’/mj OR ‘body weight’:ti,ab OR ‘total body weight’:ti,ab OR ‘body weight change*’:ti,ab OR ‘body mass’/exp. OR ‘body mass’:ti,ab OR
‘bmi’:ti,ab OR ‘body mass index’:ti,ab OR ‘quetelet* index’:ti,ab OR ‘body size’/exp. OR ‘body size’:ti,ab OR ‘fat free mass’/exp. OR ‘fat free
mass’:ti,ab OR ‘fat mass’/exp. OR ‘fat mass’:ti,ab OR ‘lean mass’:ti,ab OR ‘head circumference’/exp. OR ‘head circumference’:ti,ab OR ‘cranial
circumference’:ti,ab OR ((‘postdischarge’:ti,ab OR ‘post-discharge’:ti,ab) AND (‘growth’/mj OR ‘growth’:ti,ab)))
Web of Science TS = ((“Extremely low birth weight infant*” OR “ELBW” OR “Extremely Low Birth Weight”) AND (“Body Constitution*” OR “Body Distribution” OR
“body weights and measures” OR “Body Measure*” OR “morphometry” OR “Morphometrics” OR “Body Fat Distribution” OR “Body Fat Patterning”
OR“Adiposity” OR “Adipose tissue distribution” OR “Fat tissue distribution” OR “Fatty Tissue Distribution” OR “Body Mass Index” OR “Quetelet*
Index” OR “BMI” OR “Body Size*” OR “Body Mass” OR “Body Height*” OR “Body length” OR “Body Weight*” OR “Total Body Weight” OR
“Body Weight Change*” OR “Body Composition*” OR “body water” OR “Whole Body Water” OR “Total Water” OR “Total Body Water” OR “Total
Body Fluid” OR “Adipose Tissue*” OR “Fat Tissue” OR “Fatty Tissue” OR “Fat Pad*” OR “Body Fat” OR “body lipid” OR “visceral fat distribution”
OR“Subcutaneous Fat distribution” OR “Anthropometry” OR “Anthropometric index” OR “Anthropometrics” OR “Anthropometric parameters” OR
“Cephalometry” OR “Cephalometrics” OR “Craniometry” OR “Craniometrics” OR “Head circumference” OR “Cranial Circumference” OR “Fat
Mass” OR “Fat Free Mass” OR “Lean Mass” OR ((“Postdischarge” OR “Post-discharge”) AND “growth”)))
ELBW Extremely low birth weight, BMI Body mass index, Ti title, Ab abstract, Mh MeSH, NoExp unexploded, Tiab title or abstract, Mj major focus, Exp explode, TS top
a normal height compared with the mean biparental predicted height at 14, 15, and 20 years [36,38].
When compared with the WHO growth charts, ELBW infants seem to have a growth pattern almost similar to the 25th percentile with some values around the 5th percentile under the age of 1. Only a few stud-ies found a height that was comparable with the 50th percentile (Fig. 2).
Weight
Most studies agree that ELBW infants also remain ligh-ter than NBW infants at each corrected age (CA) [17–21, 30, 37, 39–41]. However, two studies did not find a statistical significance between former ELBW and
NBW infants at the age of 14, 20 [36], and 34 [35]. One study described a lower weight in male patients only at the age of 11 [41] and one in female patients only at the age of 14.7 [20].
In their first 7 years of life, ELBW infants seem to have a weight similar to the 25th percentile of the WHO growth charts, with a trend toward the 50th percentile afterwards (Fig.3).
Head circumference
All studies investigating HC report that ELBW infants and adolescents have a smaller HC than NBW control peers in their childhood as well as when they reach adult age [18,19, 30,37,39–41]. g ni n e er c S Included Elig ib ility n oi t ac ifi t n e dI
Records idenfied through database searching (n = 1094) Full-text arcles excluded, with reasons (n = 19) Addional records idenfied
through other sources (n = 2)
Records aer duplicates removed (n = 700) Studies included in qualitave synthesis (n = 17) Records screened (n = 700) Records excluded (n = 664) Full-text arcles assessed for eligibility
(n = 36) Fig. 1 PRISMA 2009 flow
The WHO growth charts only describe HC until the age of 5. During this period, the HC of ELBW infants seems to fluctuate between the 25th and 50th percentile with a trend toward the 25th percentile (Fig.4).
Body mass index
Since both their height and weight are lower than that of NBW children, it is still unclear whether former ELBW
Table 2 Overview of included studies
Authors and reference
Study design Group N
(male/female)
Age (N) at assessment Mean GA
(weeks)
Mean BW (grams) Measuring
methods Atkinson SA et al.
[34]
Longitudinal cohort
ELBW 125 23.1 ± 1.4y (96) 7.1 ± 2.3 841 ± 125 DEXA
NBW 119 23.5 ± 1.2y (92) NA NA
Crane JD et al. [35] Cross-sectional cohort
ELBW 29 (12/17) 34.3 ± 0.33y NA 830 ± 20 Harpenden
stadiometer Electronic scale MRI; DEXA NBW 16 (7/9) 34.9 ± 0.32y NA 3330 ± 100 Doyle LW et al. [36] Longitudinal cohort
ELBW 42 (15/27) Birth to 20.3 ± 1.0y
at 2y, 5y, 8y, 14y
27.4 ± 2.0 877 ± 86 Harpenden
stadiometer Digital scale
Hack. et al. [20] Longitudinal
cohort
ELBW 148 (52/96) 8y (147); 14y (148) 26.5 ± 2 825 ± 119/813 ± 124 Infantometer;
stadiometer
NBW 176 (65/111) 8y (176); 14y (115) ≥37 3323 ± 597/3238 ± 411
Hill AS et al. [37] Retrospective
cohort
ELBW 46 Birth; discharge; 6 m;
12 m;1 8 m
27.03 ± 1.75 796.22 ± 140.18 NA
Hirata T et al. [38] Longitudinal
cohort
ELBW 103 Follow-up from birth to
14.3 ± 1.8
(8)y / 15.6 ± 1.5y (15)
26.6 ± 1.4 818 ± 110 Standard balance
beam weight scale with height rod
Jordan IM et al. [31]
Retrospective cohort
ELBW 159 (82/77) Birth, TCA, 3 m, 9 m, 18 m,
36 m
28 ± 2 851.2 ± 116.5 NA
Kwinta P et al. [39] Cross-sectional cohort
ELBW 81 (29/52) 6.7 ± 0.4y 27.2 ± 2.1 845 ± 130 Multifrequency
bioimpedance
NBW 39 (19/20) 6.9 ± 0.8y 39.9 ± 1.4 3554 ± 512
Lin YC et al. [40] Retrospective
cohort
ELBW 100 (41/59) 6 m (68), 12 m (67), 24 m (62) 26* 772* Standard procedure
Mól N et al. [41] Prospective
cohort
ELBW 81 (29/52) 6.61 ± 0.36y (81); 11.06 ± 0.38y
(62) 27.3 ± 2.3 843.3 ± 132.4 Standard medical tape; fixed stadiometer Medical scale (nearest 100 g) NBW 36 (19/17) 6.98 ± 0.83y; 10.62 ± 0.82y 39.8 ± 1.4 3589.4 ± 538.8 Monset-Couchard M et al. [22] Longitudinal cohort
ELBW 166 (64/102) Consistent follow-up from birth
to 18 years of age NA NA NA Morrison M et al. [17] Prospective cohort
ELBW 100 (40/60) 31.63 ± 1.66y 27.10 ± 2.45 829.00 ± 130.38 Harpenden
stadiometer Electronic scale DEXA NBW 89 (37/52) 31.96 ± 1.42y NA 3391.30 ± 442.28 Peralta-Carcelen M et al. [18] Cross-sectional cohort
ELBW 53 (22/31) 14.8 ± 1.8y 28.2 ± 2.3 849 ± 109 DEXA
NBW 53 14.9 ± 1.7y >37 3355 ± 526 Raaijmakers A et al. [30] Longitudinal case-control ELBW 93 (49/44) Birth (140); 9 m (118); 24 m (96); 11.3 ± 1.4y (93) NA NA Bioelectrical impedance NBW 87 (43/44) 10.9 ± 1.3y NA NA Rodríguez-Soriano J et al. [21] Longitudinal cohort
ELBW 40 (23/17) 8.6 ± 1.8y 27.6* 845* Harpenden
stadiometer
NBW 43 (25/18) 8.5 ± 1.8y NA NA
Saigal S et al. [19] Prospective
cohort
ELBW 147 (65/82) Birth (179); 1y (157); 2y (137);
3y (123); 8y (147); 14.1 ± 1.6y (144); 23.3 ± 1.2y (147)
27.1 ± 2.3 841 ± 125 Calibrated scale
Balance beam scale
NBW 131 (59/72) 8y (145); 141.4 ± 1.3 (121);
23.6 ± 1.1y (131)
NA 3380 ± 475
Sices L et al. [42] Retrospective
cohort ELBW 154 (71/83) Birth (154); 39.2 ± 3.0w (154); 4.4 ± 0.7 m (143); 8.6 ± 1.0 m (138); 19.0 ± 1.2 m (151) 25.9 ± 1.8 768 ± 140 Harpenden infantemeter Health-o-Meter Scale N is the number of infants in the selected cohort used to determine the mean GA and BW
N at age of assessment was added when different from the initial cohort
ELBW extremely low birth weight, NBW normal birth weight, GA gestational age, w weeks, m months, y years BW birth weight, NA not available; information could not be extracted from the study, DEXA dual-energy x-ray absorptiometry
Table 3 Quality A ssessment T ool for O bs ervatio na l C ohort and Cross-Se ctional S tudies Cr ite ri a S tudy Cr ane et al . [ 35 ] Doyle etal . [ 36 ] Ha ck. et al . [ 20 ] Hi ll et al . [ 37 ] Hi ra ta et al . [ 38 ] Jordan etal . [ 31 ] Li n et al . [ 40 ] Mól etal . [ 41 ] Mons et-Couch ard et al . [ 22 ] Mor ri son et al . [ 17 ] Pe ra lt a-Ca rc ele n et al . [ 18 ] R aai jmaker s et al . [ 30 ] Rodríguez- So ri an o et al . [ 21 ] Sai g al et al . [ 19 ] Si ce s et al . [ 42 ] 1. W as the res ea rch quast ion o r objective in this p aper clearly stated? Ye s Y es Ye s Y es N o Ye s N o Y es Ye s Y es Ye s Y es Y es Y es Ye s 2. W as the st udy p opulat ion clearly spec if ied and defin ed ? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 3. W as the p ar ticip at ion rat e o f eli g ibl e pers ons at least 50%? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 4. W ere all the subjects selected or recruit ed from th e sa m e or si milar popu lati ons (in cl udi ng the same time perio d )? W er e in clusi o n and ex cl u si o nf o r b ei n gi nt h e study prespecif ied and appl ied uni form ly to all pat ients ? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 5. W as a sample si ze ju sti ficati on, power descri pti on, or var iance and ef fect estimates p rovided? Ye s N o N o N o N o N o N o N o N o N o N o N o N o N o N o 6. For the analys es in thi s paper , were the expos ure(s) of in terest measured prio r to the out come (s ) b ei n g m ea su red? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 7. W as the ti mefram e su ff icient so th at one could reason ab ly expect to see an asso ci atio n bet w ee n exp osure and out come if it exis ted? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 8. For expos ures that can vary in amount o r le vel, did th e st udy examine d if fere n t levels o f th e expo sure as re la ted to the outcome (e.g.), categories o f expos ure, o r expo sure measured as conti nuous variable)? NA N A N A NA N A NA NA NA NA NA N A N A NA NA N A 9. W ere the expos ure m easures (in d ependent vari ab les clearly d ef ined, valid , reli able, and implemented cons ist en tly across al l st udy p art ici p an ts ? Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es Ye s 10 .W as the exposu re (s ) as sessed more than once over ti m e? NA N A N A NA N A NA NA NA NA NA N A N A NA NA N A 1 1 . W ere the outcom e measures (dependent variables) clearly defin ed , v al id, reli able, and impl em en te d consis tent ly across all stu d y p articipants? Ye s Y es Ye s Y es N o Ye s Y es Ye s Y es Ye s Y es Ye s Y es Y es Y es
children achieve a BMI score that is equal to that of NBW children and adolescents [17,19,20,36], or if their BMI will be lower [21, 30, 32, 39, 41]. One study found a higher BMI score in ELBW infants, but this result did not reach statistical significance when compared to NBW control subjects [35].
Studies do not contain BMI data under the age of 6.7. By age 8 years and afterwards, BMI scores of former ELBW infants seem to reach values between the 50th and the 75th percentile of the WHO growth charts (Fig.5).
Catch-up growth patterns
Studies investigating catch-up growth commonly report that ELBW infants experience a period of neonatal growth failure from birth to TCA, which sometimes continues until 8 months or even after 1 year of age. This growth failure is followed by a period of catch-up growth, especially for weight and height, which con-tinues until adulthood [19, 20, 22, 35–38, 41, 42].
Studies do not uniformly agree on the time of onset of catch-up growth for different growth parameters and the use of different definitions makes it hard to compare the results. Some found catch-up growth starting from the age of 2 years [19], while others report catch-up growth in most subjects before the age of 3 years [22,31,42].
Former ELBW infants seem to have a marked catch-up growth in weight and height between the age of 8 and 14 years, with a more pronounced increment in weight than in height. During this period, there was also a marked catch-up growth for BMI [19,20,36].
It is suggested that catch-up growth for weight and height in the first 2 years of life or HC in the first 9 months is asso-ciated with a lower %TBF at adolescence. Catch-up growth for weight during childhood (2–11 years) was also associated with a lower %TBF at young adolescence [30]. Hack et al. however discuss that catch-up growth throughout infancy is associated with measures of obesity at the age of 14 and is therefore not beneficial [20].
SGA versus AGA
As the definition is based on a weight, a relevant portion of ELBW infants are SGA, higher than infants born with a NBW [18, 19]. After the age of 8.6 and afterwards, no significant difference in height and weight remained be-tween SGA and AGA infants, but SGA infants reached a height significantly below target height at 11 years [21]. Only one study found a significantly smaller HC in SGA ELBW infants compared to AGA ELBW infants at the age of 14 [18]. Ta bl e 3 (continued ) Cr ite ri a S tudy Cr ane et al . [ 35 ] Doyle etal . [ 36 ] Ha ck. et al . [ 20 ] Hi ll et al . [ 37 ] Hi ra ta et al . [ 38 ] Jordan etal . [ 31 ] Li n et al . [ 40 ] Mól etal . [ 41 ] Mons et-Couch ard et al . [ 22 ] Mor ri son et al . [ 17 ] Pe ra lt a-Ca rc ele n et al . [ 18 ] R aai jmaker s et al . [ 30 ] Rodríguez- So ri an o et al . [ 21 ] Sai g al et al . [ 19 ] Si ce s et al . [ 42 ] 12 . W ere th e out come ass essors bl inded to th e expos ure st atus of parti cipant s? Y es N o N o N o N o N o N o N o N o N o Y es N o No No N o 13 . W as loss to follow-up after basel ine 20% or le ss ? N A Ye s Y es Ye s N o Y es Ye s N o Y es N o Ye s Y es Y es Y es Ye s 14 . W ere k ey pot en tial confou nding v ar iables measured and adjusted st atis tical ly for thei r im p ac t on the rela tion ship b etween expos ure(s) and outcomes? Ye s Y es Ye s N o N o Y es N o N o N o Ye s Y es Ye s N o Y es Ye s CD cannot determine, NA not applicable, NR not reported
Table 4 : Mean anthropometric p aramet ers ± 1 standard deviation. Age and reference G en Height (cm) W eight (kg) BMI (kg/m 2 )H C (c m ) N ELBW(/NBW) ELBW NB W E LBW N BW ELBW NB W E LBW N B W ELBW NBW 39. 2 w ee ks CA [ 42 ] M /F 4 4 .5 ± 2 .7 NA 2.4 4 ± 0 .4 9 N A N A N A 3 3.2 ± 1 .7 N A 1 54 NA 4m o n th s [ 42 ] M /F 5 9 .3 ± 3 .1 NA 5.6 6 ± 0 .8 9 N A N A N A 4 1.1 ± 1 .5 N A 1 43 NA 6m o n th s [ 40 ] M 65 .2 ± 2 .8 NA 6 .9 ± 1. 1 N A N A N A 4 1 .9 ± 2. 1 N A 2 8 N A F 6 4.1 ± 2.6 N A 6 .5 ± 0 .9 NA NA NA 41.0 ± 1 .6 NA 40 NA 8.6 m ont hs [ 42 ] M /F 6 7 .1 ± 3 .1 NA 7.4 0 ± 1 .0 4 N A N A N A 4 3.9 ± 1 .5 N A 1 38 NA 11 m o n th s [ 19 ]M 70.2 ± 4 .3 N A 7 .7 ± 1 .3 NA NA NA 4 5 .3 ± 1 .8 NA 7 3 -7 4 N A F 6 9.6 ± 4 .4 N A 7 .6 ± 1 .2 NA NA NA 4 4 .2 ± 1 .7 NA 8 0 -8 3 N A 12 m onth s [ 40 ] M 73 .7 ± 4 .0 NA 8 .5 ± 1. 1 N A N A N A 4 4 .5 ± 1. 6 N A 2 6 2 6 F 7 2 .9 ± 2 .6 N A8 .1 ± 1 .1 8 N AN AN A 4 3 .7 ± 1 .8 N A 4 1 N A 19 m onth s [ 42 ] M /F 7 9 .6 ± 3 .5 NA 9.9 8 ± 1 .4 2 N A N A N A 4 6.6 ± 1 .6 N A 1 51 NA 23 m onth s [ 19 ] M 8 2 .9 ± 4 .2 NA 10. 4 ± 1.6 N A N A N A 4 7.8 ± 1 .9 N A 6 4-66 NA F 8 1.8 ± 3 .9 N A 10. 2 ± 1.5 N A N A N A 4 6.9 ± 1 .4 N A 7 0-71 NA 2y ea rs [ 40 ] M 8 5 .1 ± 5 .2 NA 10. 7 ± 1.8 N A N A N A 4 6.5 ± 2 .3 N A 2 8 N A F 8 4.9 ± 3 .2 N A 10. 7 ± 1.5 N A N A N A 4 5.9 ± 1 .8 N A 3 4 N A 34 m onth s [ 19 ] M 9 1 .1 ± 5 .0 NA 12. 2 ± 1.7 N A N A N A 4 9.3 ± 1 .8 N A 5 6-59 NA . F 9 0 .4 ± 4 .6 NA 12. 2 ± 1.7 N A N A N A 4 7.9 ± 1 .5 N A 5 6-64 NA 6.7 /6. 9 y ea rs [ 39 ] M /F 1 1 5.3 ± 7 1 2 4 .5 2 ± 7.3 9 19. 7 ± 4,7 2 5.2 3 ± 5 .3 5 1 4.6 ± 2 .2 1 6 .16 ± 2 .34 4 9.6 ± 2 .2 5 2 .2 ± 1. 33 8 1 3 6 7.8 /ye ar s [ 19 ] M 1 21. 7 ± 7.8 1 2 8 .2 ± 5 .7 22. 5 ± 4.7 2 7.3 ± 5 .0 N A N A 5 1.5 ± 1 .5 5 3 .3 ± 1. 4 6 7 6 6 F 1 20. 9 ± 6.1 1 2 8 .1 ± 5 .7 21. 9 ± 3.4 2 7.8 ± 5 .2 N A N A 5 0.6 ± 1 .4 5 2 .7 ± 1. 5 8 0 7 9 8 /9. 2 y ear s [ 20 ] M 1 26. 6 ± 8.8 1 3 3 .4 ± 8 .0 28. 1 ± 10. 8 3 3.1 ± 1 0 .4 1 7 .1 ± 4 .2 * 18 .3 ± 4 .2 * NA NA 52 42 . F 1 28. 7 ± 8.3 1 3 6 .2 ± 8 .3 29. 3 ± 9.0 3 5.2 ± 1 1 .2 1 7 .4 ± 4 .0 * 18 .6 ± 4 .2 * NA NA 96 73 8.6 /8. 5 y ea rs [ 21 ] M /F 1 2 6 ± 12 13 1 ± 15 26 ± 7 3 4 ± 9 1 6 .0 ± 2 .3 19 .3 ± 2 .7 NA NA 4 0 4 3 11 y ea rs [ 41 ] M /F 1 41. 7 ± 7.8 3 14 6.2 6 ± 8 .8 1 33. 88 ± 8 .315 3 9 .9 ± 9 .3 1 6 .7 4 ± 3.2 6 18 .72 ± 3 .4 5 1.3 7 ± 2 .2 4 5 4 .02 ± 1 .42 6 2 3 6 1 1 .3 y10 .9 ye ar s* * [ 30 ] M /F 1 45. 1 ± 9.3 1 4 9 .2 ± 1 0.1 36. 7 ± 9.6 3 9.9 ± 9 .3 1 7.0 ± 2 .8 1 7 .7 ± 2. 5 5 1.7 ± 1 .8 5 3 .4 ± 1. 6 9 3 8 7 14. 1/1 4 .4 y ea rs [ 19 ] M 1 58. 3 ± 14. 4 1 6 7 .4 ± 1 0.9 48. 7 ± 14. 3 5 9.6 ± 1 4 .7 NA NA 5 4 .3 ± 2 .1 56 .6 ± 1 .6 6 3 -6 5 5 2-53 F 1 54. 2 ± 7.5 1 6 1 .9 ± 6 .8 48. 1 ± 1 1 .7 5 6 .2 ± 1 0.5 N A N A 5 3.6 ± 1 .8 5 5 .6 ± 2. 0 7 8-79 6 8 14. 7/1 4 .8 y ea rs [ 20 ] M 1 64. 0 ± 9.4 * 16 7.1 ± 7 .6 * 58. 5 ± 21. 0 * 63 .0 ± 1 8 .0 * 2 1 .4 ± 6 .1 * 22 .4 ± 5 .5 * NA NA 52 42 F 1 56. 8 ± 6.2 1 6 1 .9 ± 6 .1 56. 6 ± 15. 1 6 3.2 ± 1 9 .3 2 2 .9 ± 5 .6 * 24 .0 ± 6 .8 * NA NA 96 73 14. 8/1 4 .9 y ea rs [ 18 ] M /F 1 60. 5 ± 9.3 1 6 5 .3 ± 8 .2 55. 3 ± 15. 0 6 4.4 ± 1 6 .1 NA NA 5 4 .7 ± 2 .1 56 .0 ± 1 .9 5 3 5 3 14. 3 y ea rs [ 38 ] M 1 72. 0 ± 21. 2 N A 51. 3 ± 10. 9 N A N A 5 5 .1 ± 1. 7 N A 8 NA 15. 6 y ea rs [ 38 ] F 1 59. 7 ± 6.7 N A 56. 6 ± 8.7 N A N A N A 5 4 ± 1.7 N A 1 5 N A 23. 3/2 3 .6 y ea rs [ 19 ] M 1 70. 6 ± 9.5 1 7 7 .8 ± 7 .8 70. 7 ± 14. 9 7 7.2 ± 1 4 .6 2 4 .2 ± 4 .6* 2 4 .4 ± 4. 4 5 6.3 ± 1 .8 5 7 .8 ± 1. 4 6 5 5 9 . F 1 58. 3 ± 6.8 1 6 4 .5 ± 6 .7 60. 1 ± 13. 6 6 7.2 ± 1 6 .0 2 4 .0 ± 5 .6* 2 4 .8 ± 5. 3 5 4.1 ± 1 .6 5 5 .8 ± 2. 0 8 2 7 2 31. 63/ 31. 96 ye ar s [ 17 ] M /F 1 6 4 ± 10 17 1 ± 1 1 71. 90 ± 1 6 .54 7 7 .5 0 ± 18. 28 2 6 .9 1 ± 6.4 1 * 2 6 .49 ± 5 .08 N A N A N A 1 00 34. 3/3 4 .9 y ea rs [ 35 ] M /F 16 4 ± 2 1 71 ± 3 7 3 .8 ± 2 .8 * 72 ± 4 .1 27 .4 ± 1 .0 * 2 4. 5 ± 1 .0 N A N A 2 9 1 6 Height, w eight, B MI and H C are re pr ese n te d for ag e. * p > 0 .05; no significant dif ference between E LBW and NBW in fan ts ** p < 0 .05; dif ference in height, w eig h t and BMI w as st ill si gnif ica nt af te r correcting for age EL B W extremely low birth w eight, NBW normal b irth weight, BMI body mass ind ex, HC head circumference, NA not available; data that could not be extracted from the study ,G en gend er , M male, F fe ma le ,N number o f p articipants in the ELBW or NBW g roup.
Body composition
FM, LM, and relative body composition
Two studies report a lower %LM or lean mass index (LMI, i.e., total lean mass/height2), with a higher %TBF and fat mass index (FMI, i.e., total fat mass/height2) in ELBW infants [17, 30]. The third study found a higher %TBF in male infants only [34]. Otherwise, a fourth study found a significantly lower absolute LM and FM, but also a lower %TBF in children born with an ELBW at the age of 7 [39].
The fifth study found no significant difference in %TBF and %LM between ELBW and NBW infants reaching the age of 14. They conclude that ELBW infants have a lower FM and LM, but that the relative body composition is similar to those of NBW children [18] (Table5).
There was no difference in body composition between SGA and AGA ELBW infants [18,30].
Fat distribution
Only one study and one abstract reported on fat distribution in ELBW infants with different results since ELBW infants had a higher portion of visceral adipose tissue deposition in one study [34], and this higher portion was limited to the subcu-taneous fat areas only in the other study [35]. The last report also found higher proportions of pancreatic and liver fat in ELBW infants reaching young adulthood, but an ELBW was not an independent influencer of these fat fractions [35]. Body water
Two studies investigated body water in ELBW infants, with contradictory results. One study found lower absolute TBW but a higher %TBW in former ELBW infants [39], while the other found no significant difference in %TBW between ELBW and NBW infants [30].
Discussion
Children born as ELBW infants have a specific growth pattern until birth and exhibit a different body composition at birth and TCA than their NBW counterparts. Their compromised growth may result in a body composition later in life that differs from NBW children. Literature describing growth and evolution of body composition after hospital discharge and in later life, however, is scarce. Therefore, we performed a systematic literature search regarding growth parameters and body composition in former ELBW infants throughout child-hood and adolescence.
Most studies state that ELBW infants remain smaller and lighter than NBW infants at every stage of their
Table 5 Bo dy compos ition: FM, % TBF , LM, % LM ± 1 st andard deviation A g e (year s) and ref ere n ce Gen F at ma ss (kg) %T BF Le an mass (kg ) %L M N ELBW/N BW ELBW NBW E LBW N BW ELBW NBW E LB W N BW ELBW NBW 6.7/6.9 [ 39 ] M/ F 2.4 ± 1.98 4.3 ± 0.76 1 1 .3 ± 7 .5 16.3 ± 8.15 17.3 ± 2.66 20.3 ± 3.64 NA NA 81 39 11 .3 /10.9** [ 30 ] M/ F NA NA 24.6 ± 9.8 19.2 ± 0.1 N A N A 75.1 ± 10.2 80.5 ± 8 .9 9 3 8 7 14.8/14.9 [ 18 ] M/ F 13.09 ± 8 .82 17.20 ± 9 .58 23.09 ± 10.99* 25.99 ± 1 0.74 38. 81 ± 10.19 43.40 ± 9 .72 72.72 ± 10.62* 69.93 ± 10.40 53 53 23.1/25.3 [ 34 ] M NA NA 20.3 ± 6.6 16.6 ± 5.2 N A N A N A N A 4 1 4 0 F NA NA 30.6 ± 7.1* 29.0 ± 6.4 N A N A N A N A 5 5 5 2 31.63/31.96 [ 17 ] M/ F NA NA 35.45 ± 10.81 30.75 ± 1 0.49 NA NA NA NA 100 89 FM, T B F , L M and % L M are represented for age. *P > 0 .0 5 **P < 0 .05: results were still signi ficant after correction for age EL B W extr emely low bir th w ei ght, NBW normal b irth weight, FM fa t m ass, %TBF percentage total bod y fat, LM lea n mass, %LM per cent age le an ma ss, NA not availab le; data that could not be extracted from the study , Ge n gender , M male, F fe ma le
development. In two studies, ELBW infants attained their predicted biparental target height [36, 38]. Although catch-up growth is often described, ELBW infants still attain lower growth parameters by the time they reach adulthood. Since their growth restriction is expressed both in weight and height, it is not clear whether their BMI at
teen and adult age significantly differs from that of NBW infants or not. It is suggested that catch-up growth is more pronounced for weight than for height (“stunting”), resulting in infants being proportionally heavier for their height, although former ELBW infants are never assumed to have a significantly higher BMI score [20, 32,36]. Fig. 2 Height for age. Height for age is plotted for ELBW infants. The
shaded areas represent the 5th–25th and 25–50th percentiles of the WHO growth charts;ELBW function: General model Rat44: f(x) = (p1*x^4 + p2*x^3 + p3*x^2 + p4*x + p5) /, (x^4 + q1*x^3 + q2*x^2 + q3*x + q4),
Coefficients (with 95% confidence bounds): p1 = 204.5 (−159.7,
568.8), p2 =−2524 (−1.05e+04, 5452), p3 = −2966 (−2.332e+05,
2.272e+05), p4 = 5.533e+05 (−4.751e+06, 5.858e+06), p5 = 1.924e+05 (−1.825e+06, 2.21e+06), q1 = 2.602 (−197.4, 202.6), q2 = −432.9
(−5454, 4588), q3 = 6270 (−5.07e+04, 6.324e+04), q4 = 4312
(−4.087e+04, 4.95e+04), Goodness of fit: SSE: 36.72;R2: 0.999;
Adjusted R2: 0.9984; RMSE: 1.62; SSE sum of squared estimate of errors,
RMSE root mean square error
Fig. 3 Weight for age. Weight for age is plotted for ELBW infants. The
shaded areas represent the 5th–25th and 25th–50th percentiles of the
WHO/CPEG growth charts and the 3th–25th percentiles of the extended
charts provided by the CPEG;ELBW function: General model Rat45:
f(x) = (p1*x^4 + p2*x^3 + p3*x^2 + p4*x + p5) /; (x^5 + q1*x^4 + q2*x^3 + q3*x^2 + q4*x + q5); where x is normalized by mean 9.043 and std. 10.21; Coefficients (with 95% confidence bounds): p1 =
5.146e+06 (−3.084e+11, 3.084e+11); p2 = 9.356e+06 (−5.607e+11,
5.607e+11); p3 = 4.198e+06 (−2.516e+11, 2.516e+11); p4 = 9.184e+05
(−5.504e+10, 5.505e+10); p5 = 8.684e+05 (−5.204e+10, 5.204e+10);
q1 = 4.386e+04 (−2.628e+09, 2.628e+09); q2 = 1.847e+05 (−1.107e+
10, 1.107e+10); q3 = 7.957e+04 (−4.768e+09, 4.768e+09); q4 =
−1.152e+04 (-6.898e+08, 6.898e+08); q5 = 3.429e+04 (−2.055e+09,
2.055e+09); Goodness of fit: SSE: 32.65; R2: 0.9972; Adjusted R2:
0.9949; RMSE: 1.723; SSE sum of squared estimate of errors, RMSE root mean square error
Former ELBW infants do not only reach a lower target height and weight at every CA but they also have a smaller HC. It has been suggested that a smaller HC is related to poorer cognitive outcomes [43–45], but one study investigat-ing neurodevelopment did not find an association between catch-up growth for HC and neurocognitive outcome [30].
When comparing with the WHO growth charts, we came to similar results, especially for height and HC. ELBW infants
seem to attain a height around the 25th percentile at young adult age. Their HC also seems to be around the 25th percen-tile. In the first 7 years of life, their weight and BMI remain around the 25th percentile with afterwards a trend toward the 50th percentile. Their BMI seems to reach values between the 50th and the 75th percentile by young adulthood.
In the studies that linked catch-up growth to adverse health outcomes, there is no consensus whether early catch-up growth is Fig. 4 Head circumference for age. Head circumference for age is plotted
for ELBW infants. The shaded areas represent the 5th–25th and 25–50th
percentiles of the WHO growth charts;ELBW function: General model
Rat24: f(x) = (p1*x^2 + p2*x + p3) / ; (x^4 + q1*x^3 + q2*x^2 + q3*x +
q4); Coefficients (with 95% confidence bounds): p1 =−4439 (−3.263e+
05, 3.174e+05); p2 = 1.478e+06 (−4.638e+06, 7.593e+06); p3 = 4.502e+
05 (−1.222e+06, 2.123e+06); q1 = 32.91 (−70.88, 5.063); q2 = 27.98
(−7218, 7274); q3 = 2.934e+04 (−9.444e+04, 1.531e+05); q4 = 1.349e+
04 (−3.662e+04, 6.359e+04); Goodness of fit: SSE: 5.773; R2
: 0.99;
Adjusted R2: 0.9845; RMSE: 0.7244; SSE sum of squared estimate of
errors, RMSE root mean square error
Fig 5 BMI for age. BMI for age is plotted for ELBW infants. The shaded
areas represent the 25th–50th, 50–75th, and 75th–95th percentiles of the
WHO growth charts;ELBW function: General model Rat34: f(x) = (
p1*x^3 + p2*x^2 + p3*x + p4) /; (x^4 + q1*x^3 + q2*x^2 + q3*x + q4);
Coefficients (with 95% confidence bounds): p1 = 2361 (−1.199e+06,
1.203e+06); p2 = 87.87 (−4.044e+11, 4.044e+11); p3 = 857.6
(−1.361e+11, 1.361e+11); p4 = 225.7 (−1.909e+11, 1.909e+11); q1 =
7.852 (−1.713e+08, 1.713e+08); q2 = 1665 (−1.279e+09, 1.279e+09);
q3 =−4398 (−2.848e+11, 2.848e+11); q4 = −1901 (−8.607e+11,
8.607e+11); Goodness of fit: SSE: 9.316; R2: 0.9557; Adjusted R2:
0.8008; RMSE: 2.158; SSE sum of squared estimate of errors, RMSE root mean square error
beneficial for metabolic and cardiovascular diseases, hyperten-sion, and renal function later in life or not [12,19,20,30].
With regard to body composition and fat distribution in ELBW infants, there remains some controversy. Studies do not agree on differences in %LM, FM, %TBF and fat distri-bution [17,18,30,34,35,39].
It is suggested that an aberrant body composition with a higher %TBF could indeed make ELBW infants and adoles-cents more susceptible to cardiovascular diseases and insulin resistance [17,30,34].
Nevertheless, there is a lack in information about the body composition in former ELBW infants and it is possible that differences in body composition and fat distribution only ap-pear with advancing age, thus there is a need for longitudinal studies [17]. There is also no agreement on the ideal measure method to investigate body composition.
There are some limitations to this review as a result of the inclusion of long-term follow-up studies and the comparison of cases at different points of time.
Some of the study patients were born in the 1990s or ear-lier. Perinatal care and nutritional practices have since evolved, so one should be careful extrapolating these results to the current population of ELBW neonates [17,18].
Another consequence of including longitudinal follow-up studies is a certain degree of loss of follow-up for part of the subjects, which could cause bias in the remaining study population.
Furthermore, because we did not have access to individual growth data in the different studies, we focused on mean data. Studies also use different definitions of SGA and often do not compare the GA of SGA and AGA infants. This is an import limitation, as SGA infants will have a higher GA per definition and might therefore exhibit a different growth pattern. Nevertheless, the results in most of the studies so far do not show a significant difference in growth parameters between SGA and AGA infants after the age of 8.6, but former SGA infants often represent the smallest spectrum of ELBW infants later in life. One more main limitation is the assessment at many different time points and the heterogeneity of the study populations.
Future studies should investigate the correlation between growth, weight gain, and adipose tissue development since not only ELBW but also BMI is suggested to be a possible influencer of body composition and related adverse health outcomes [17].
Intervention studies should focus on proportional growth and weight gain, especially from the age of 8 until the age of 14. However, increase in height and weight during this period might be influenced by inadequate growth in the first years of life. Also, catch-up growth for height and weight in the first 2 years of life might be beneficial for body composition later in life [19,20,30,36,41]. Careful follow-up throughout child-hood is therefore needed to optimize the growth patterns of ELBW infants.
Conclusion
Studies consistently report that ELBW infants attain lower growth parameters than NBW control patients after hospital discharge throughout childhood and adolescence. Although there seems to be a certain degree of catch-up growth for all growth parameters, differences in anthropometric parameters continue to exist with advancing age. Since catch-up growth is often more pronounced for weight than for height, it is impor-tant to strive for proportional growth in intervention studies.
There is a lack of studies investigating body composition in ELBW infants. There is some evidence that they might have an aberrant body composition, but studies do not draw uni-form conclusions. Associations between body composition and cardiovascular diseases are suggested. Further research and longitudinal studies are needed to ascertain whether the higher prevalence of metabolic and cardiovascular diseases could indeed be a consequence of an aberrant growth pattern, different body composition, or inadequate fat tissue development.
Authors’ Contributions Both authors drafted the study and were involved
in the study design. C.V.d.P. performed the systematic review. In case of uncertainties, the second author was consulted. Both authors wrote the final manuscript and approved the manuscript.
Funding There is no funding source.
Compliance with ethical statements
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Conflict of interest The authors declare that they have no conflict of
interest, and there was no specific funding for this project.
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